Research Project
Grant-in-Aid for Scientific Research (C)
There is growing clinical interest of thalidomide because of its immunomodulatory and antiangiogenic properties, despite its teratogenicity. However, little information about thalidomide has been reported regarding its precise effects on drug-metabolizing enzymes. We investigated the effects of thalidomide on cytochrome P450(P450) enzymes in human liver microsomes to clarify the potential for possible drug interactions. The present results suggest that total midazolam metabolism or cyclosporine A clearance may be increased by thalidomide in a dose-dependent manner. Unexpected drug interactions involving thalidomide might occur via heterotropic cooperativity of polymorphic P450 3A5.We investigate these drug interactions in cultured human liver cell line system more closely resembled livers. A new hepatic cell line system with differentiated HepaRG cryopreserved(Biopredic International, Rennes, France) was adopted. These results suggest that cultured human cell line system with differentiated HepaRG cryopreserved could be applicable to thalidomide drug interaction study. Further oxidative metabolism of 5-hydoroxythalidomide to 5-hydroxythalidomide GSH-conjugate formation is under investigation using the new HepaRG cell system mimicking in vivo human livers.
All 2012 2011 2010 2009 Other
All Journal Article (29 results) (of which Peer Reviewed: 29 results) Presentation (14 results) Remarks (4 results)
J. Biosci. Bioeng
Volume: 111 Pages: 78-84
110008440354
Drug Metab. Dispos
Volume: 39 Issue: 4 Pages: 724-728
10.1124/dmd.110.036780
J. Health Sci
Volume: 57 Pages: 164-170
130000663115
http://dx.doi.org/10.1248/jhs.57.164
Volume: 39 Issue: 5 Pages: 757-762
10.1124/dmd.110.037853
Drug Metab. Lett
Volume: 5 Pages: 216-219
Drug Metab Pharmacokinet
Volume: 26 Pages: 532-7
130004463217
http://dx.doi.org/10.2133/dmpk.DMPK-11-RG-039
Curr Drug Metab
Volume: 12 Pages: 549-69
Volume: 12 Pages: 412-35
Drug Metab.Dispos.
Volume: 39 Issue: 4 Pages: 717-723
10.1124/dmd.110.036574
Brit.J.Pharmacol.
Volume: 163 Issue: 6 Pages: 1250-1262
10.1111/j.1476-5381.2011.01341.x
Mice Chem Res Toxicol
Volume: 24 Issue: 3 Pages: 287-289
10.1021/tx200005g
Drug Metab.Lett
Drug Metabolism and Pharmacokinetics
Volume: 26 Issue: 5 Pages: 532-537
10.2133/dmpk.DMPK-11-RG-039
J.Pharmacol.Exp.Ther
Volume: 339 Issue: 2 Pages: 654-661
10.1124/jpet.111.185009
J.Health Sci.
J.Biosci.Bioeng
Volume: 39 Pages: 74-728
Chem. Res. Toxicol
Volume: 23 Pages: 1018-1024
Regul Toxicol Pharmacol
Volume: 58 Pages: 252-8
Chem. Res. Toxicol.
Volume: 23 Issue: 12 Pages: 1921-1935
10.1021/tx100286d
130004639911
Chem.Res.Toxicol.
Volume: 56 Pages: 557-565
130000425091
Chem.Res.ToxicoL
Volume: 24 Pages: 287-289
Drug Metab.Pharmacokinet. (印刷中)
10027583437
Xenobiotica 39
Pages: 227-235
Drug Metab.Pharmacokinet. 24
Pages: 404-408
Chem.Res.Toxicol. 22
Pages: 1325-1333
Drug Metab.Lett.t. 3
Pages: 207-211
Curr.Drug Metab. 10
Pages: 700-712
http://www.shoyaku.ac.jp/labosite/doutai/index.html
http://www.shoyaku.ac.jp/labosite/doutai